This application was filed under 35 USC 371 as the national phase of PCT/AU96/00167, Mar. 25, 1996.
The present invention relates to methods for regulating processes of microorganisms. In particular, methods and culture media including furanones for inhibiting homoserine lactone (HSL) and/or acylated homoserine lactone (AHL) regulated processes in microorganisms.
Microorganisms, including bacteria, fungi and algae, have a profound effect upon the activities of humans and animals. Considerable efforts have been made to find compounds and methods for the control of such micro organisms. There is a need to continually find new compounds and methods for this purpose is due, in part at least, to the capacity of such microorganisms to rapidly mutate to circumvent the compounds and methods already developed.
One set of fundamental regulator agents which are widespread in bacteria, including human pathogens, are known as homoserine lactones (HSL) or acylated homoserine lactones (AHL). The AHL regulatory systems in bacteria are two component regulatory systems which regulate intercellular activity in response to environmental conditions and extracellular signal molecules. This system was first discovered in the bioluminescent marine bacteria Vibrio harveyi and V. fischeri where it is used to control expression of bioluminescence. In principle, the system is comprised of two proteinsxe2x80x94LuxR and LuxI. The LuxI enzyme is encoded by a luxI gene and produces a related family of signal molecules known as the homoserine lactones. These signal molecules bind to the LuxR regulator which is then activated and serves both as a positive regulator for the structural genes which encode the enzymes responsible for bioluminescence, and as a positive regulator for the luxI gene itself. The entire system is amplified via a process of auto induction. Additional molecules serve as regulators of the LuxR-LuxI system.
While initially discovered for bioluminescent bacteria, this regulatory system has now been found in numerous other microorganisms, and is involved in a wide variety of bacterial activities (Swift et al. 1994. Fuqua et al. 1994). These activities include, but are not restricted to, exoenzyme production in the plant pathogen Erwinia carotovora and in Pseudomonas aeruginosa, the causative agent of cystic fibrosis, and Ti plasmid transfer from Agrobacterium tumefaciens to plants. In all instances, acylated homoserine lactone, or homoserine lactone-like compounds are the regulatory auto inducers.
Since these regulatory systems are widespread among bacteria, and because they control processes leading to bacterial invasion of host organisms, it is likely that other organisms will have evolved defence mechanisms against these systems. So far none have been found. The present inventors have now developed methods of inhibiting microbial processes using compounds that are mimics of the homoserine lactone family of regulatory compounds.
In a first aspect, the present invention consists of a method of inhibiting a homoserine lactone and/or acylated homoserine lactonexe2x80x94regulated process in a microorganism comprising exposing the microorganism to a furanone compound so as to inhibit the process.
In a second aspect, the present invention consists of a microbial culture medium for inhibiting a homoserine lactone and/or acylated homoserine lactonexe2x80x94regulated process in a microorganism, the medium comprising growth and/or maintenance ingredients and a furanone compound.